The thioredoxin system: Balancing redox responses in immune cells and tumors

Abstract

The thioredoxin (TRX) system is an important contributor to cellular redox balance and regulates cell growth, apoptosis, gene expression, and antioxidant defense in nearly all living cells. Oxidative stress, the imbalance between reactive oxygen species (ROS) and antioxidants, can lead to cell death and tissue damage, thereby contributing to aging and to the development of several diseases, including cardiovascular and allergic diseases, diabetes, and neurological disorders. Targeting its activity is also considered as a promising strategy in the treatment of cancer. Over the past years, immunologists have established an essential function of TRX for activation, proliferation, and responses in T cells, B cells, and macrophages. Upon activation, immune cells rearrange their redox system and activate the TRX pathway to promote proliferation through sustainment of nucleotide biosynthesis, and to support inflammatory responses in myeloid cells by allowing NF-κB and NLRP3 inflammasome responses. Consequently, targeting the TRX system may therapeutically be exploited to inhibit immune responses in inflammatory conditions. In this review, we summarize recent insights revealing key roles of the TRX pathway in immune cells in health and disease, and lessons learnt for cancer therapy.

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system

“…TrxR is a redox protein that maintains the redox ratio of the cellular system 45 . The breast cancer cells express the TrxR redox system 25 .…”

“…TrxR is a redox protein that maintains the redox ratio of the cellular system. 45 The breast cancer cells express the TrxR redox system. 25 The inhibition of the TrxR-mediated redox system enhances the cytotoxicity of chemotherapeutic drugs and radiation.…”

Cysteine-binding adjuvant enhances survival and promotes immune function in a murine model of acute myeloid leukemia

“…In this work, we leveraged the characteristic redox imbalance of AML 25 , 57 , 58 to preferentially adjuvant tumor cells and debris via their exofacial free thiols for in situ vaccination via IV administration. We found that the redox imbalance is further exacerbated by cytarabine treatment, 59 associated with Trx-1 expression, improving binding of our polymer to cancer cells.…”

Exploring the Molecular Tapestry: Organ-Specific Peptide and Protein Ultrafiltrates and Their Role in Therapeutics

“…Thus, it is involved in maintaining the cell’s status and adapting to changes in the redox environment—an essential aspect of many biological processes, including DNA synthesis and repair and cell growth and death. It might have potential therapeutic applications in supporting immune responses under healthy conditions [ 43 ].…”